Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District,Tianjin 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.
J Ethnopharmacol. 2021 Dec 5;281:114438. doi: 10.1016/j.jep.2021.114438. Epub 2021 Aug 11.
Compound Danshen Dripping Pill (CDDP), composed of Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H. Chen and Borneol, is a famous traditional Chinese medicine formula which has made great achievements in the treatment of ischemic heart disease, but the profound mechanism of CDDP improving post ischemic myocardial inflammation hasn't been clearly discussed.
The aim of this study was to explore the biological mechanism of constituents in CDDP synergistically improving post ischemic myocardial inflammation.
The pharmacologic studies were applied to assess the cardio protection effect of CDDP in acute myocardial ischemic rats. To identify the anti-inflammatory ingredients in CDDP, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with a dual-luciferase reporter assay for NF-κB inhibition were used. The network pharmacology and molecular docking assay were adopted to predict targets of anti-inflammatory ingredients and then the regulation effects of these active components on their targets were also verified.
Our results indicated that CDDP exerted an excellent cardio protection effect by reversing echocardiographic abnormalities, attenuating histopathological lesion, ameliorating circulating myocardial markers and inflammation cytokines. Tanshinol, salvianolic acid B (Sal B), tanshinone IIA (Tan IIA) and notoginsenoside R1 (NGR1) were the pivotal anti-inflammatory ingredients in CDDP. The anti-inflammatory mechanism is that tanshinol and Sal B respectively targeted on PPARγ and JNK, while Tan IIA worked on AKT1 and NGR1 bound to PI3K.
Our results firstly demonstrated that CDDP effectively ameliorated post ischemic myocardial inflammation through simultaneously modulating MAPK, PI3K/AKT and PPAR pathways in a multi-components synergetic manner.
复方丹参滴丸（CDDP）由丹参、三七和冰片组成，是一种著名的中药方剂，在治疗缺血性心脏病方面取得了巨大成就，但 CDDP 改善缺血后心肌炎症的确切机制尚未得到明确讨论。
本研究旨在探讨 CDDP 中各成分协同改善缺血后心肌炎症的生物学机制。
采用药理研究评估 CDDP 在急性心肌缺血大鼠中的心脏保护作用。为了确定 CDDP 中的抗炎成分，采用超高效液相色谱/四极杆飞行时间质谱联用双荧光素酶报告基因检测 NF-κB 抑制作用。采用网络药理学和分子对接技术预测抗炎成分的靶点，并验证这些活性成分对其靶点的调节作用。
我们的结果表明，CDDP 通过逆转超声心动图异常、减轻组织病理学损伤、改善循环心肌标志物和炎症细胞因子，发挥出色的心脏保护作用。丹参醇、丹参酸 B（Sal B）、丹参酮 IIA（Tan IIA）和三七皂苷 R1（NGR1）是 CDDP 中的关键抗炎成分。抗炎机制是丹参醇和 Sal B 分别靶向 PPARγ和 JNK，而 Tan IIA 作用于 AKT1，NGR1 与 PI3K 结合。
我们的研究结果首次表明，CDDP 通过同时调节 MAPK、PI3K/AKT 和 PPAR 通路，以多成分协同方式有效改善缺血后心肌炎症。
